China
Africa
Explore chapters and articles related to this topic
Marginal Zone Lymphoma
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
The chromosome translocations occur at markedly variable incidences in MALT lymphoma of different sites, but are always mutually exclusive [20,60]. For chromosomal gain at 9q34, Zhou et al. [59] suggested that TRAF2 and CARD9 may be the target genes. Both genes have been shown to interact with BCL10 and activate NF-κB. Partial inactivation of the p53 gene may play a role in the development of low-grade MALT lymphoma [61], whereas complete inactivation may be associated with high-grade transformation (similar to other hematologic malignancies) [49]. Homozygous deletions of p16 also play a role in large cell transformation [49]. Transformation of MALT lymphoma to DLBCL occurs in ~8% (more frequently in extranodal lymphomas of MALT type than in nodal and splenic MZLs) and is proceeded by the emergence of increased numbers of transformed blasts that form sheets or clusters on histologic examination [15,40,41,43]. Gastric MALT lymphoma usually remains localized for long periods within the tissue of origin. BM involvement at presentation is uncommon [19,23]. Disseminated disease appears to be more common in non-GI MALT lymphomas [43,62].
Principles of the WHO classification with special reference to aggressive extranodal lymphomas
Published in Franco Cavalli, Harald Stein, Emanuele Zucca, Extranodal Lymphomas, 2008
Harald Stein, Michael Hummel, Lorenz Trümper, Nancy Lee Harris
Nuclear factor Kappa B (NF-κB) expression and, as a consequence, the up-regulation of many NF-κB target genes is a hallmark of ABC-like DLBCL cases. Although constitutive NF-κB up-regulation is also found in several other lymphoma entities, the mechanism for this activity appears to be different among the various lymphoma types. In ABC-like DLBCL, the activation of NF-κB is mediated by the upstream molecules CARMA1, BCL10, and/or MALT1, which, in turn, activate the IKKs, leading to degradation of the NF-κB inhibitors.32 This leads to the release of NF-κB into the nucleus and to the expression of the NF-κB target genes.
Very-Early Onset Chronic Active Colitis with Heterozygous Variants in LRBA1 and CARD11, a Case of “Immune TOR-Opathies”
Published in Fetal and Pediatric Pathology, 2023
Mai He, Amanda Wong, Kimberly Sutton, Mercia Jeanne Bezerra Gondim, Charles Samson
Caspase activation and recruitment domain 11 (CARD11) is an adaptor protein in lymphocytes that facilitates signal transduction downstream of T cell or B cell receptor activation to initiate activation of NF-κB and other signaling pathways through forming a scaffold called CBM (CARD11-BCL10-MALT1) signalsome complex [18]. Multiple different types of variants for CARD11 have been described, each of which leads to the development of different clinical phenotypes [19,20]. To validate novel gene variants for pathogenicity, functional assays could be performed utilizing a CARD-11 deficient Jurkat T cell line expressing an NF-κB GFP reporter [19]. Mutations affecting the CARD11-BCL10-MALT1 (cbm) signalosome complex are associated with an abnormal activation of the mtor/s6k signaling pathway [6]. It is true that this variant may be novel as a cause of VEO-IBD, although in a study of severe atopic disease due to different CARD11 mutations, 3 of 8 patients had GI manifestations including eosinophilic proctocolitis in an 18 month old (other two patients were teenagers with ulcerative colitis and chronic diarrhea, respectively) [21]. Another study suggested that the CARD family, including CARD11, was likely to be involved in inflammatory bowel disease [22].
Development of molecular intervention strategies for B-cell lymphoma
Published in Expert Review of Hematology, 2021
Cystatin recruitment domain (CARD) 9 and CARD11 drive the activation of immune cells by binding to BCL-10 and triggering its translocation into the nuclei. However, these proteins are in a state of automatic inhibition before stimulation. This automatic inhibition region includes a wide interface between its CARD and curly coil domain. The destruction of this interface will lead to over-activation of CARD11 in cells and the formation of BCL-10 template filaments. Finally, BCL-10 and MALT1 form protein complexes to regulate the activation of NF-κB, and C-Jun N-terminal kinase (JNK) when induced by an antigen receptor. This is very important for the activation and proliferation of lymphocytes and the development of specific types of B-cells [85–87] (Figure 4). Studies have shown that inhibition of NF-κ B and JNK signaling pathways downstream of the CARD11/BCL-10/MALT-1 (CBM) complex can lead to B-cell death in vitro, while BTK, PI3K, and SYK inhibitors do not inhibit B-cell proliferation [87]. Therefore, direct inhibition of the CBM complex or its downstream signaling pathway may be a potential treatment for CARD11 mutant lymphoma; IKB kinase (IKK) inhibitors may be considered for NF-κ B signaling pathway.
Caspase-1 inhibition by YVAD generates tregs pivoting IL-17 to IL-22 response in β-glucan induced airway inflammation
Published in Immunopharmacology and Immunotoxicology, 2022
Divyesh Patel, Naveen Challagundla, Dipeeka Mandaliya, Shivani Yadav, Omkar Naik, Parameswar Dalai, Dhruvi Shah, Hima Vora, Reena Agrawal-Rajput
Invasive aspergillosis is one of the common invasive fungal infections in immunosuppressed hosts with a mortality rate of 58% [1]. Fungal allergen can trigger symptoms ranging from rhinitis to allergic bronchopulmonary aspergillosis (ABPA) [2]. Aspergillus, a common environmental fungus, colonizes at lower respiratory tract and represent persistent allergen. Repeated exposure of such allergen leads to allergic airway diseases [3]. ABPA is most commonly accompanied by lung disorder such as asthma [2,4]. β-glucan, a major component of fungal cell wall is recognized by Dectin-1 receptor of innate immune and lung epithelial cells [5]. Dectin-1 is a C-type lectin receptor having extracellular carbohydrate recognition domain and cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) like-domain [6]. Upon β-glucan binding, tyrosine phosphorylation of ITAM initiates intracellular signaling by recruiting spleen tyrosine kinase (SYK). SYK kinase activates (i) NF-kB signaling through activation of CARMA-BCL10-MALT1 (CBM) scaffold [7,8]; and (ii) NLRP3/Caspase-1 inflammasome mediated IL-1β secretion [9]. Dectin-1 also activates SYK-independent signaling pathway to activate several noncanonical NF-kB subunits and several other transcription factors [8]. All these inflammatory pathways culminate to exacerbated production of inflammatory cytokines thus causing bystander tissue damage. Importantly, IL-1β mediated Th17 differentiation leads to high IL-17 expression in aspergillosis which have been correlated with disease pathology in both infectious and allergic settings [10]. So, inhibiting Th17 differentiation provides a better strategy to control inflammation mediated tissue damage.